HER2-enriched subtype and pathological complete response in HER2-positive breast cancer: A systematic review and meta-analysis

Francesco Schettini, Tomás Pascual, Benedetta Conte, Nuria Chic, Fara Brasó-Maristany, Patricia Galván, Olga Martínez, Barbara Adamo, Maria Vidal, Montserrat Muñoz, Aranzazu Fernández-Martinez, Carla Rognoni, Gaia Griguolo, Valentina Guarneri, Pier Franco Conte, Mariavittoria Locci, Jan C. Brase, Blanca Gonzalez-Farre, Patricia Villagrasa, Sabino De PlacidoRachel Schiff, Jamunarani Veeraraghavan, Mothaffar F. Rimawi, C. Kent Osborne, Sonia Pernas, Charles M. Perou, Lisa A. Carey, Aleix Prat

Research output: Contribution to journalReview article

Abstract

Background: HER2-positive (HER2+) breast cancer (BC) comprises all the four PAM50 molecular subtypes. Among these, the HER2-Enriched (HER2-E) appear to be associated with higher pathological complete response (pCR) rates following anti-HER2-based regimens. Here, we present a meta-analysis to validate the association of the HER2-E subtype with pCR following anti-HER2-based neoadjuvant treatments with or without chemotherapy (CT). Methods: A systematic literature search was performed in February 2019. The primary objective was to compare the association between HER2-E subtype (versus others) and pCR. Selected secondary objectives were to compare the association between 1) HER2-E subtype and pCR in CT-free studies, 2) HER2-E subtype within hormone receptor (HR)-negative and HR+ disease and 3) HR-negative disease (versus HR+) and pCR in all patients and within HER2-E subtype. A random-effect model was applied. The Higgins’ I2 was used to quantify heterogeneity. Results: Sixteen studies were included, 5 of which tested CT-free regimens. HER2-E subtype was significantly associated with pCR in all patients (odds ratio [OR] = 3.50, p < 0.001, I2 = 33%), in HR+ (OR = 3.61, p < 0.001, I2 = 1%) and HR-negative tumors (OR = 2.28, p = 0.01, I2 = 47%). In CT-free studies, HER2-E subtype was associated with pCR in all patients (OR = 5.52, p < 0.001, I2 = 0%) and in HR + disease (OR = 4.08, p = 0.001, I2 = 0%). HR-negative status was significantly associated with pCR compared to HR + status in all patients (OR = 2.41, p < 0.001, I2 = 30%) and within the HER2-E subtype (OR = 1.76, p < 0.001, I2 = 0%). Conclusions: The HER2-E biomarker identifies patients with a higher likelihood of achieving a pCR following neoadjuvant anti-HER2-based therapy beyond HR status and CT use. Future trial designs to escalate or de-escalate systemic therapy in HER2+ disease should consider this genomic biomarker.

Original languageEnglish
Article number101965
JournalCancer Treatment Reviews
Volume84
DOIs
Publication statusPublished - Mar 2020

Keywords

  • Biomarker
  • Breast cancer
  • HER2-Enriched
  • HER2-positive
  • PAM50
  • Pathologic complete response

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

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    Schettini, F., Pascual, T., Conte, B., Chic, N., Brasó-Maristany, F., Galván, P., Martínez, O., Adamo, B., Vidal, M., Muñoz, M., Fernández-Martinez, A., Rognoni, C., Griguolo, G., Guarneri, V., Conte, P. F., Locci, M., Brase, J. C., Gonzalez-Farre, B., Villagrasa, P., ... Prat, A. (2020). HER2-enriched subtype and pathological complete response in HER2-positive breast cancer: A systematic review and meta-analysis. Cancer Treatment Reviews, 84, [101965]. https://doi.org/10.1016/j.ctrv.2020.101965